Stroke, one of the three most common diseases in China, is a neurological disease characterized by transient or permanent brain dysfunction. Ischemic stroke is the most important form of stroke. The main manifestation of ischemic stroke is the injury, death and eventual loss of brain function of nerve cells caused by ischemia and hypoxia. Neurons have very limited self-renewal or regeneration ability when damaged or injured in adulthood. The golden rule of clinical treatment for stroke patients: Revascularization of the responsible vessels within the effective time window (usually within 6 hours of onset) is the key to successful treatment. However, there are still nearly half of the patients with acute occlusion of intracranial large blood vessels can not be significantly improved or even worse after surgery due to various reasons such as poor blood flow compensation. Therefore, for patients who miss the "effective treatment time window" and most of whom have no significant postoperative cure effect, it is more necessary for us to start from the overall prevention of stroke, control various risk factors, actively search for the pathogenesis, and carry out targeted drug therapy for the pathogenesis, and explore and dig the disease prevention and treatment strategy of stroke from the root and source.

On December 15, 2022, Tong Xiaoping Research Team of Songjiang Research Institute of Shanghai Jiaotong University School of Medicine, in collaboration with the research team of Wan Jieqing Affiliated to Renji Hospital, they published an online study entitled "Kir4.1 channel activation in NG2 glia contributes to remyelination" in eBioMedicine, a subsidiary of the international authoritative journal Lacent "in ischemic stroke". This study is the first to show that Kir4.1 ion channel protein levels are significantly reduced in patients with acute ischemic stroke, and that these patients have severe axonal demyelination in the ischemic penumbra and cerebral cortex infarct areas. Through the mouse transient middle cerebral artery obstruction disease model (tMCAO), the study further found that the defect of Kir4.1 ion channel expressed by NG2 glial cells is the key factor leading to the loss of axon myelin. NG2 (Oligodendrocyte precursor cells, OPCs, oligodendrocyte), the fourth type of glial cells in the central nervous system, have extremely unique biological characteristics. NG2 glial cells are widely distributed in the brain and remain relatively stable in number. NG2 glial cells in mature brain have two important functions: 1. As an independent glial cell, NG2 glial cells interact with neurons and integrate into the neural circuit to function. 2, maintain the potential of proliferation and differentiation, in myelin damage (such as demyelinating disease, brain injury) when oligodendrocytes play a nerve repair function. The researchers tried and found a natural Chinese herbal compound called luteolin that can cross the blood-brain barrier and cause Kir4.1 ion channels to open. Treatment with luteolin in mice with cerebral ischemia disease can increase the Kir4.1 channel current of NG2 glial cells, further promote the myelin regeneration of axons, reduce the cerebral infarction area of mice, and ultimately improve the neuromotor function of mice.

In this study, transgenic technology, visual whole-cell patch clamp recording, transmission electron microscopy, small animal nuclear magnetic resonance imaging, in vivo behavioral analysis and other experimental techniques were used to improve the neuromotor function of ischemic stroke model mice through Kir4.1 potassium ion channels targeting glial cells, so as to provide clinical drug development and therapeutic application for cerebral stroke diseases. It provides new ideas and strategies.

The illustration on the left is an artistic illustration of the study, inspired by the Chinese myth "Nuwa Mending the sky". Severe axonal demyelination damage occurs in stroke patients, and "day" means the brain; With the help of the natural Chinese herbal compound Luteolin, through the activation of potassium ion channel Kir4.1, the "day" can be completed, promote the repair of motor function, and improve the neurological function of the brain.

Tong Xiaoping, Researcher, Songjiang Research Institute, Department of Anatomy and Physiology, Shanghai Jiaotong University School of Medicine, and Wan Jieqing, Director of the affiliated Renji Hospital are co-corresponding authors. Hong Xiaoqi, Assistant researcher, School of Basic Medicine, Shanghai Jiaotong University, Jian Yujin, graduate student, and Ding Shenghao, deputy chief physician, Renji Hospital, are co-first authors of this paper. The research was supported by the National Ministry of Science and Technology, the National Foundation Committee, the Shanghai Municipal Education Commission, the Shanghai Municipal Science and Technology Commission, and the high-level innovation team of the School of Medicine of Shanghai Jiao Tong University.

Article link:

https://authors.elsevier.com/sd/article/S2352396422005886